Neural cell adhesion molecule modulates mesenchymal stromal cell migration via activation of MAPK/ERK signaling

• Published in: Experimental cell research 2012-10, Vol.318 (17), p.2257-2267
• Main Authors: Shi, Yu, Xia, Yin-Yan, Wang, Lei, Liu, Rui, Khoo, King-Shung, Feng, Zhi-Wei
• Format: Article
• Language: English
• Subjects: Adipocytes - cytology; Adipocytes - metabolism; Animals; Blotting, Western; Bone marrow; CD56 Antigen - physiology; Cell adhesion & migration; Cell Adhesion - physiology; Cell Differentiation; Cell Movement - physiology; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Flow Cytometry; Gene expression; Immunoenzyme Techniques; Male; MAP Kinase Signaling System - physiology; MAPK/ERK signaling; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Migration; MSCs; NCAM; Osteogenesis; Phosphorylation - drug effects; Real-Time Polymerase Chain Reaction; Receptors, Fibroblast Growth Factor - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal transduction; Stem cells; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2012.05.029

Mesenchymal Stromal Cells (MSCs) represent promising tools for cellular therapy owing to their multipotentiality and ability to localize to injured, inflamed sites and tumor. Various approaches to manipulate expression of MSC surface markers, including adhesion molecules and chemokine receptors, have been explored to enhance homing of MSCs. Recently, Neural Cell Adhesion Molecule (NCAM) has been found to be expressed on MSCs yet its function remains largely elusive. Herein, we show that bone marrow-derived MSCs from NCAM deficient mice exhibit defective migratory ability and significantly impaired adipogenic and osteogenic differentiation potential. We further explore the mechanism governing NCAM mediated migration of MSCs by showing the interplay between NCAM and Fibroblast Growth Factor Receptor (FGFR) induces activation of MAPK/ERK signaling, thereby the migration of MSCs. In addition, re-expression of NCAM180, but not NCAM140, could restore the defective MAPK/ERK signaling thereby the migration of NCAM deficient MSCs. Finally, we demonstrate that NCAM180 expression level could be manipulated by pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-α treatment. Overall, our data reveal the vital function of NCAM in MSCs migration and differentiation thus raising the possibility of manipulating NCAM expression to enhance homing and therapeutic potential of MSCs in cellular therapy. ► Bone marrow-derived MSCs from NCAM deficient mice exhibit defective migration. ► Lack of NCAM leads to impaired adipogenic and osteogenic differentiation of MSCs. ► Activation of MAPK/ERK signaling contributes to NCAM mediated MSC migration. ► NCAM180 isoform plays a dominate role in MSCs migration regulation. ► NCAM180 expression level could be manipulated by TNF-α treatment.